Fenofibrate Delays the Need for Dialysis and Reduces Cardiovascular Risk Among Patients With Advanced CKD

Abstract

Context Fenofibrate provides limited cardiovascular (CV) benefits in the general population; however, little is known about its benefit among advanced chronic kidney disease (CKD) patients. Objective This study compared outcomes among advanced CKD patients treated with fenofibrate, statins, a combination of both, and none of these. Design National cohort study Setting Taiwan’s National Health Insurance Research Database Patients Aged >20 years with advanced CKD were identified and further divided into 4 groups according to treatment. The inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Intervention Patients received fenofibrate, statins, a combination of fenofibrate and statins, or none of these in the 3 months preceding the advanced CKD date. Main outcome measures All-cause mortality, CV death, and incidence of permanent dialysis Results The fenofibrate and statin groups exhibited a lower risk of CV death (fenofibrate vs. nonuser: HR: 0.84, 95%CI: 0.75-0.94; statins vs nonuser: HR: 0.94, 95%CI: 0.90-0.97) compared with the nonuser group. The fenofibrate group further exhibited the lowest incidence of permanent dialysis (fenofibrate vs. nonuser: SHR: 0.78, 95% CI: 0.77-0.80; statins vs. fenofibrate: SHR: 1.27, 95%CI: 1.26-1.29; combination vs. fenofibrate: SHR: 1.15, 95%CI: 1.13-1.17). Furthermore, the combined administration of fenofibrate and high intensity statins exhibited a lower risk of MACCEs. Conclusions For patients with advanced CKD, continuing fenofibrate may provide a protective effect on CV outcomes equal to that of statins, and it may further delay the need for permanent dialysis. The combination of fenofibrate and high intensity statins may have additional benefits.

Use of fibrates is not associated with reduced risks of mortality or cardiovascular events among ESRD patients: A national cohort study

“…Patients without previous diagnosis of any kind of hyperlipidemia, with incomplete demographics, who were younger than 20 years, or who had undergone renal transplantation prior to the index date were excluded. The remaining patients were divided into four groups (fibrate, statin, combination, and non-user groups) according to their use of lipid-lowering medications within 3 months prior to the index date ( 19 ). In Taiwan, cholestyramine is not available, and, according to NHI's regulations, ezetimibe and niacin could only be prescribed with statin for patients who are difficult to achieve treatment target under statin alone.…”

“…Because of such concerns, the use of fibrates for the treatment of dyslipidemia in CKD population remains limited. Studies have evaluated the effectiveness of fibrates in reducing CV risk in populations with mild to moderate ( 14 , 17 , 18 ) and advanced ( 19 ) CKD. However, few studies have evaluated the effectiveness of fibrates in reducing CV risk in patients with ESRD.…”

Fatty kidney: A possible future for chronic kidney disease research

“…Significant improvement in renal oxidative stress, renal function and proteinuria has been recorded with fenofibrate in mice, but no clinical studies have yet investigated the effects of PPAR‐alpha agonists on renal lipid deposition 126 . However, there is evidence supporting kidney protection by fenofibrate from large observational studies and post hoc analysis of randomized clinical trials 127,128 . In the national cohort of Taiwan's National Health Insurance Research Database, the fenofibrate group exhibited the lowest incidence of permanent dialysis (fenofibrate vs nonuser: subdistribution HR [SHR]: 0.78; 95% CI, 0.77–0.80; statins vs fenofibrate: SHR: 1.27; 95% CI, 1.26–1.29; statin‐fenofibrate combination vs fenofibrate: SHR: 1.15; 95% CI, 1.13–1.17) 128 .…”

“…However, there is evidence supporting kidney protection by fenofibrate from large observational studies and post hoc analysis of randomized clinical trials 127,128 . In the national cohort of Taiwan's National Health Insurance Research Database, the fenofibrate group exhibited the lowest incidence of permanent dialysis (fenofibrate vs nonuser: subdistribution HR [SHR]: 0.78; 95% CI, 0.77–0.80; statins vs fenofibrate: SHR: 1.27; 95% CI, 1.26–1.29; statin‐fenofibrate combination vs fenofibrate: SHR: 1.15; 95% CI, 1.13–1.17) 128 . A post hoc analysis of 2636 participants in the fenofibrate arm and 2632 in the placebo arm in the ACCORD Lipid Trial disclosed that during a median follow‐up of 4 years, treatment with fenofibrate was associated with lower rate of eGFR decline (−0.28 ml/min per 1.73 m 2 per year in the fenofibrate group vs. −1.25 ml/min per 1.73 m 2 per year in the placebo group, p < 0.01) and with lower incidence of microalbuminuria (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.43–0.72, p < 0.001) and macroalbuminuria (HR 0.72, 95% CI 0.57–0.91, p < 0.001), although there was no difference in incidence of CKD (HR 0.92, 95% CI 0.74–1.15, p = 0.46) and/or kidney failure (HR 0.95, 95% CI 0.68–1.33, p = 0.76) 127 .…”

Dyslipidemia in Chronic Kidney Disease: Contemporary Concepts and Future Therapeutic Perspectives

“…A meta-analysis conducted in 2012 reported a lower risk of cardiovascular events and mortality in fibrate users with mild-to-moderate CKD [58]. In a recently reported cohort study of patients with advanced CKD, a cardiovascular risk reduction was reported in the fenofibrate treatment arm while also protecting against incident renal function worsening [59]. Potential nephroprotective mechanisms involve attenuated oxidative stress, inflammation, and apoptosis [60].…”